The Cytomechanics Core is designed to support the University of Delaware's concerted multi-disciplinary focus on the study of osteoarthritis (OA), a major public health concern. Aside from the large socioeconomic burden, the pain and disability associated with OA greatly impacts the quality life of patients. The development of OA involves multiple factors including age, genetics, and mechanical factors. During phases I and II of the UD COBRE program, we have made great strides in understanding the role of mechanical forces in OA development and treatment of this pathology at the molecular, cellular, tissue, joint, and whole body levels. Cytomechanics is fundamental for normal cell and tissue function and disease development. The cell, the universal basic unit of life, behaves as a mechanical living entity. In addition to sense of smell or taste mediated by chemical reactions, cells also display a strong sense of touch mediated by mechanical interactions. Thus, the mechanical environment drives many fundamental processes such as cell shape, mobility, growth, differentiation, and cell fate determination. In OA, many important remain unanswered, such as (1) how mechanical forces are transduced from systemic locomotion and physical activity to local tissue and cellular stresses, (2) how cells in healthy or diseased native joint tissues respond and adapt to the mechanical environment, (3) how to use our knowledge of tissue and cell mechanics to design pharmaceutical interventions or rehabilitation protocols to treat OA, (4) how to achieve real-time and closed-loop control of cell and tissue mechanics and behavior during tissue engineering. To meet these scientific needs, we have designed this Cytomechanics Core with state-of-the-art imaging techniques and precise mechanical manipulation tools that have been acquired during previous COBRE funding years and will continue to be built upon by our COBRE team.